Apc002

Apc002: The nucleic acid aptamer targeting Dickkopf1 (DKK1) (Patent is being processed by NTD Patent & Trademark Agency Ltd.). DKK1 played an important role in tumor development, bone metastasis and other advanced invasions. Potential indications of targeting DKK1 included gastric cancer, esophageal cancer, and tumor bone metastases（Chu et al., Front Immunol 2021; Jiang et al., Front Pharmacol 2022). Elevated levels of DKK1 were detected in multiple cancers and frequently associated with poor prognosis and short disease-free survival. In phase II clinical trials, a therapeutic antibody against DKK1 C domain had additive efficacy in combination therapy with an immune checkpoint inhibitor, but demonstrated limited potency in monotherapy. In previous studies, the company research teamfound that the interaction between N domain and Linker 2 domain could facilitate the binding of C domain to downstream receptors to enhance the immunosuppressive tumor microenvironment (TME) mediated by DKK1 C domain. In addition, the company research teamfound that simultaneously knocking out C domain and the interaction sites between N and Linker 2 domains could achieve the highest anti-tumor potency. Therefore, a nucleic acid aptamer Apc002-1 that specifically targeted the interaction sites between N and Linker 2 domain and a nucleic acid aptamer Apc002-2 that specifically targets C domain were screened, designed and synthesized by the company research team. Compared with the monoclonal antibody targeting DKK1 C domain, the combination of Apc002-1 and Apc002-2 demonstrated significantly higher antitumor efficacy in animal models. The Aptacure is planning to expand the application of Apc002 in more orphan drug indications for cancer therapy. Concluding the activity characterization, the applications of Orphan Drug Designation for Apc002 will be submitted.

 

Reference 

  1. Chu HY, Chen ZH, Wang LY, Zhang ZK, He YX, Zhang BT. Lyu AP, Yu YY, Zhang G. (2021).The Dickkopf-1: a promising target for cancer immunotherapy. Front Immuno.12:658097.

  2. Jiang, H., Zhang, Z., Yu, Y., Chu H., Y., Yu, S., Yao, S., Zhang, G. & Zhang, BT. (2022). Drug discovery of DKK1 inhibitors. Front. Pharmacol. 13, 847387-847387.